title: Cortex Dictamni extract induces apoptosis of activated hepatic stellate cells via STAT1 and attenuates liver fibrosis in mice.
abstract: BACKGROUND
  In traditional Chinese medicines, Cortex Dictamni is prescribed for the treatment of a variety of inflammatory diseases such as acute rheumatoid arthritis, skin inflammation and jaundice.
  
  
  OBJECTIVE
  This study was designed to investigate the effect of ethanol extract of Cortex Dictamni on treatment of hepatic fibrosis and its possible mechanisms.
  
  
  METHODS
  The in vivo effect of Cortex Dictamni extract (CDE) was evaluated by measuring histological changes and collagen content in CCl(4)-indcued hepatic fibrosis mice. Viability, apoptosis and protein expression of hepatic stellate cells (HSC) were analyzed by MTT, Annexin V staining and Western blot respectively.
  
  
  RESULTS
  CDE alleviated CCl(4)-induced hepatic fibrosis in mice and showed a much stronger inhibition of cell viability in activated HSC cell line HSC-T6 than that in normal hepatocyte L02 cells. Furthermore, CDE induced apoptosis of HSC-T6 cells associated with increased expressions of cleaved PARP and cleaved caspase-3. Interestingly, CDE activated STAT1 in HSC-T6 cells and the effect of CDE on apoptosis of HSC-T6 cells could be neutralized using JAK/STAT1 signaling inhibitor AG490.
  
  
  CONCLUSIONS
  These findings suggest that CDE possesses anti-fibrosis activity with selectively induction of activated HSC apoptosis via activating STAT1, which might be a novel strategy for hepatic fibrosis therapy.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing, Jiangsu 210093, China.
authors.forename: Xing-Xin
authors.initials: XX
authors.lastname: Wu
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Wu
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Fan
authors.forename: Yu
authors.initials: Y
authors.lastname: Qin
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002251:Carbon Tetrachloride; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D036905:Dictamnus; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008517:Phytotherapy; D024301:Plant Bark; D018517:Plant Roots; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D004365:Drugs, Chinese Herbal; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D002251:Carbon Tetrachloride; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3